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Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.
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@#Objective To explore the feasibility and clinical value of free-of-puncture positioning in three-dimension-guided anatomical segmentectomy for ground-glass nodule (GGN) compared with percutaneous positioning. Methods Clinical data of 268 enrolled patients undergoing anatomical pulmonary segmentectomy from October 2018 to June 2019 were retrospectively collected, including 75 males and 193 females with an average age of 56.55±12.10 years. The patients were divided into two groups, including a percutaneous positioning group (n=89) and a free-of-puncture positioning group (n=179). Perioperative data of the two groups were compared. Results The average CT scan times of the percutaneous positioning group was 3.01±0.98 times, and the numerical rating scale (NRS) score of puncture pain was 3.98±1.61 points. Pulmonary compression pneumothorax (≥30%) occurred in 7 (7.87%) patients and intercostal vascular hemorrhage occurred in 8 (8.99%) patients after puncture. Lung nodules were successfully found and removed in both groups. There was no statistically significant difference between the two groups in the location of nodules (P=0.466), operation time (151.83±39.23 min vs. 154.35±33.19 min, P=0.585), margin width (2.07±0.35 cm vs. 1.98±0.28 cm, P=0.750), or the number of excised subsegments (2.83±1.13 vs. 2.73±1.16, P=0.530). Conclusion Anatomical segmentectomy with three-dimensional navigation avoids the adverse consequences of puncture, which has the same clinical efficacy and meets the requirements of oncology compared with percutaneous positioning. The free-of-puncture positioning method can be used for GGN located in the central region of pulmonary segment/subsegment or adjacent to intersegment veins instead of percutaneous positioning.
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@#Objective To analyze the difference of location identification of pulmonary nodules in two dimensional (2D) and three dimensional (3D) images, and to discuss the identification methods and clinical significance of pulmonary nodules location in 3D space. Methods The clinical data of 105 patients undergoing sublobectomy in the Department of Thoracic Surgery, the First Affiliated Hospital with Nanjing Medical University from December 2018 to December 2019 were analyzed retrospectively. There were 28 males and 77 females, with an average age of 57.21±13.19 years. The nodule location was determined by traditional 2D method and 3D depth ratio method respectively, and the differences were compared. Results A total of 30 nodules had different position identification between the two methods, among which 25 nodules in the inner or middle zone of 2D image were located in the peripheral region of 3D image. The overall differences between the two methods were statistically significant (P<0.05). The diagnostic consistency rates of two methods were 66.67% in the right upper lung, 83.33% in the right middle lung, 73.68% in the right lower lung, 75.76% in the left upper lung, and 64.71% in the left lower lung. In each lung lobe, the difference between the two methods in the right upper lung (P=0.014) and the left upper lung (P=0.019) was statistically significant, while in the right middle lung (P=1.000), right lower lung (P=0.460) and left lower lung (P=0.162) were not statistically significant. Conclusion The 3D position definition of lung nodules based on depth ratio is more accurate than the traditional 2D definition, which is helpful for preoperative planning of sublobectomy.
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BACKGROUND@#For early-stage lung cancer, segmentectomy can get the same oncological benefits as lobectomy. Accurate identification of the intersegmental border is the key to segmentectomy. This study used extended segmentectomy and extended subsegmentectomy to treat lung intersegmental and intersubsegmental ground-glass nodules (GGN) by utilizing modified inflation-deflation methods to distinguish the intersegmental and intersubsegmental borders. The accuracy of modified inflation-deflation methods and the effectiveness of extended resection to guarantee a safe surgical margin were evaluated.@*METHODS@#A retrospective analysis of 83 cases of extended segmentectomy and extended subsegmentectomy was conducted. Preoperative three-dimensional computed tomography bronchography and angiography (3D-CTBA) revealed that nodules were involved in intersegmental or intersubsegmental veins. Based on preoperative three-dimensional reconstruction, the surgery was designed to extendedly remove the dominant lung segment or subsegment with nodules involved. When the dominant lung segment or subsegment could not be identified, the simpler lung segment or subsegment was selected for the resection. After the target vessel and bronchus were cut off during the operation, modified inflation-deflation method was used to determine the border, and a stapler was used to resect the adjacent lung segment or subsegment tissue by 2 cm-3 cm around the inflation-deflation boundary line. Then, the relationship between the inflation-deflation boundary line and the nodule and the width of the surgical margin were measured. Clinical data were collected during the perioperative period.@*RESULTS@#56 extended segmentectomies and 27 extended subsegmentectomies were performed. The average diameter of pulmonary nodules was (0.9±0.3) cm. There were 79 cases with clearly inflation-deflation boundary lines. The average time needed for the appearance of the lines was (13.6±6.5) min. In 55 cases, the nodules were involved with the inflation-deflation boundary lines. Meanwhile, the remaining 24 cases revealed an average minimum distance of (0.6±0.3) cm between nodules and the boundary lines. The average width of surgical margin was (2.1±0.3) cm in these 79 cases. No deaths or major complications appeared during 30 d after operation.@*CONCLUSIONS@#The modified inflation-deflation method can effectively define the intersegmental and intersubsegmental borders, and guarantee the safe surgical margins of extended segmentectomy and extended subsegmentectomy to treat intersegmental and intersubsegmental small lung tumors.
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Objective To investigate the differential expression of annexin A4 (ANXA4)protein in different phenotype of human hepatocellular carcinoma (HCC) tissues, and discuss the correlative clinico-pathologic significance. Methods The mRNA levels of ANXA4 in different liver tissues were validated by using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), and the expressions of ANXA4 protein in different liver tissues specimens were observed by immunohistochemistry assay. The relative analysis between the results of immunohistochemistry assay and the clinicopathologic parameters were studied. Results In mRNA level, the results from RT-PCR were significantly increased of ANXA4 in HCC tissues than that in cirrhosis tissues and normal liver tissues. Immunohistochemistry assay of different type liver tissues also confirmed that ANXA4 protein overexpressed in HCC tissues than that in the cirrhosis tissues post hepatitis B and normal liver tissues (49.4% vs 28.0% vs 24.0%), and the higher positive rate could be observed in different phenotype HCC tissues (53.8% in small HCC, 64.5% in large HCC, 28.6% in multiple HCC, respectively),according the positive rate of para-tumorous tissues was 53.8%, 64.5% and 67.9%, respectively. The results of statistics analysis showed that the expression of ANXA4 up-regulated gradually going with the hepatocellular malignant metaplasia and tumorous progression, but the expression of ANXA4 down-regulated when invasion were emerging in HCC. Furthermore, expression of ANXA4 had a negative correlation with the tumor size and maybe responsible for carcinogenesis and progression in human hepatocellular carcinoma. Conclusions The mRNA level of ANXA4 is significantly increased in HCC and cirrhosis tissues compared to the normal liver tissues by semi-quantitative RT-PCR. The same trend can be observed in immunohistochemistry assay. ANXA4 might be concerned with the carcinogenesis of HCC. Unbalance of expression of ANXA4 could be observed in different phenotype HCC tissues. ANXA4 might take part in the process of progression and invasion of HCC.
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Objective To evaluate the diagnosis and treatment of malignant rectal gastrointestinal stromal tumor.Methods The clinical and pathological data of 26 patients with malignant rectal gastrointestinal stromal tu- mor were retrospectively analyzed.Results All the patients underwent operation.In 13 cases Miles operation was done and 3 cases Park operation was done.The 10 patients received Dixon resection.The 3-,5-year survival rate were 73% and,54 %,respectively.The median survival time for 26 patients was 52 months.Immunohistochemical analysis displayed positive reactivity for CD117(96%) and CD34(85%).Conclusion For the malignant rectal gas- trointestinal stromal tumor,the most worthwhile diagnostic criterion was the presence of CD117 and CD34 cells and surgical radical resection is the principal treatment.